ABSTRACT
The synthesis of retinal analogue series that contain a spyropyran moiety instead of a trimethylcyclohexene ring was proposed. The process of the retinal analogue interaction with bacterioopsin from apomembranes of Halobacterium salinarum and the spectral properties of the newly formed pigments were studied. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2008, vol. 34, no. 2; see also http://www.maik.ru.
Subject(s)
Bacteriorhodopsins/chemistry , Benzopyrans/chemical synthesis , Halobacterium salinarum/metabolism , Indoles/chemical synthesis , Nitro Compounds/chemical synthesis , Retinaldehyde/analogs & derivatives , Retinaldehyde/chemical synthesis , Bacteriorhodopsins/metabolism , Benzopyrans/chemistry , Benzopyrans/metabolism , Cell Membrane/metabolism , Indoles/chemistry , Indoles/metabolism , Nitro Compounds/chemistry , Nitro Compounds/metabolism , Pigments, Biological/biosynthesis , Retinaldehyde/metabolism , StereoisomerismABSTRACT
A method of simultaneous one-stage synthesis of three retinal derivatives (5,6-dioxo-5,6-seco-, 5,6-dihydro-5,6-epoxy-, and 4-oxoretinal) was proposed, with the yield of the first derivative being approximately 50%. These compounds are useful tools for studying the antitumor activity of retinoids, the reconstituted bacteriorhodopsin analogues with changed parameters of photocycle, and the reactivity of retinal derivatives in the processes of oxidation by molecular oxygen. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2002, vol. 28, no. 6; see also http://www.maik.ru.
Subject(s)
Cyclohexanes/chemistry , Retinaldehyde/analogs & derivatives , Retinaldehyde/chemical synthesis , Esters/chemistry , Magnetic Resonance Spectroscopy , Oxidation-Reduction , Retinaldehyde/chemistry , Tretinoin/chemistryABSTRACT
A method for synthesis of retinal analogs labeled with electron-density groups is suggested. The interaction of these polyene compounds with bacterioopsin in apomembrane of Halobacterium salinarum was tested. A retinal analog containing a crown-ether receptor group is able to interact readily with bacterioopsin giving rise to rapid formation of a pigment with absorption maximum at 460 nm. This pigment is capable of undergoing cyclic photoconversion. The crown-bacteriorhodopsin photocycle is extremely slow and its quantum efficiency is very low (approximately 3% of that in native bacteriorhodopsin). This photocycle includes an M-like intermediate with a differential absorption maximum at 380 nm. A retinal analog in which the beta-ionone ring is replaced by ferrocene moiety forms a stable chromoprotein with the main absorption band at 483 nm and a shoulder near 590-610 nm.
Subject(s)
Bacteriorhodopsins/chemistry , Bacteriorhodopsins/metabolism , Electrons , Magnetic Resonance Spectroscopy , Mass SpectrometryABSTRACT
Incorporation of 9-cis-13-demethylretinal into bacterioopsin was shown to form the covalent purple complex. This result was predicted by our hypothesis about the structure of the BR chromophore cavity (Mol. Biologiya 29:1398-1407 (1995) (in Russian)). It supports the hypothesis and eliminates the main objection known from the literature.
Subject(s)
Bacteriorhodopsins/analogs & derivatives , Bacteriorhodopsins/drug effects , Bacteriorhodopsins/chemical synthesis , Bacteriorhodopsins/chemistry , Colorimetry , Gramicidin/pharmacology , Hydrogen-Ion Concentration , Models, Chemical , Retinaldehyde/analogs & derivatives , Retinaldehyde/chemistry , Retinaldehyde/pharmacology , Structure-Activity Relationship , TemperatureABSTRACT
A number of substituted pyridylisoxazoles and their 4,5-dihydro analogs were synthesized by 1,3-dipolar cycloaddition of substituted nitrile oxides to either alkenes or alkynes. The synthesized compounds inhibit arachidonic acid-induced aggregation of human thrombocytes at concentrations of 10(-6) to 10(-3) M. Due to low toxicity, these compounds can be regarded as potential antithrombosis medicines.
Subject(s)
Oxazoles/chemistry , Platelet Aggregation Inhibitors/chemical synthesis , Arachidonic Acid/physiology , Humans , Platelet Aggregation Inhibitors/chemistryABSTRACT
Several retinoids with modified polar group were synthesized. Biological screening using HL-60 promyelocyte leukemia cells showed that the free carboxyl in the retinoid molecules is not the only group responsible for exhibiting the differentiating activity.
Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Retinoids/chemical synthesis , Retinoids/pharmacology , Antineoplastic Agents/chemistry , Cell Differentiation/drug effects , HL-60 Cells , Humans , Protein Conformation , Receptors, Retinoic Acid/chemistry , Retinoids/chemistry , Spectrophotometry, InfraredABSTRACT
5,6-Epoxy-, 4-methoxy-, 4-hydroxy-, and 3,4-dehydrobacteriorhodopsins can generate delta psi coupled to a photochemical cycle with intermediate M. The kinetics of delta psi comprises three main electrogenic phases: the fast small negative, the microsecond, and the millisecond positive phases. The photocycle efficiency is lower in all the analogs. The photocycle is modified insignificantly only in 3,4-dehydrobacteriorhodopsin. In the other pigments the decay of the flash-induced bleaching in the chromophore main absorption band is slower than the decay of M or long-wave intermediates, especially in the 4-hydroxy analog. In the latter analog, such distinctions, according to delta pH measurements, are partly due to deceleration of the decay of the novel intermediate (P). In 5,6-epoxybacteriorhodopsin, at all wavelengths, the decay of the intermediates takes seconds upon M formation. According to our and literature data, no bacteriorhodopsin analogs are known to have a cycle which preserves the M-intermediate and does not transport a proton.
